Novel Zinc(II) and Copper(II) Complexes of 2-((2-Hydroxyethyl)amino)quinoline-3-carbaldehyde for Antibacterial and Antioxidant Activities: A Combined Experimental, DFT, and Docking Studies

Abstract

In the present work, two novel complexes of zinc(II) and copper(II) were synthesized from the ligand 2-((2-hydroxyethyl)amino)quinoline-3-carbaldehyde (H ₂ L) in a 1:2 metal-to-ligand ratio in methanol. The complexes were characterized by UV-visible spectroscopy, fluorescence spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, and thermogravimetric analysis (TGA) experimental techniques and density functional theory (DFT) calculations. The spectral data revealed that the mono-deprotonated (HL) ligand acted as a bidentate ligand, which bound to both Zn(II) and Cu(II) ions via the nitrogen atom of the amine (N-H) and the hydroxyl (O-H) groups through the deprotonated oxygen atom. Formation constants and thermal analysis indicated that both metal complexes are stable up to 100 °C with thermodynamically favored chemical reactions. The Cu(II) complex showed antibacterial activities with the zones of inhibition of 20.90 ± 2.00 mm against Pseudomonas aeruginosa, 19.69 ± 0.71 mm against Staphylococcus aureus, and 18.58 ± 1.04 mm against Streptococcus pyogenes. These results are relatively higher compared with the Zn(II) complex at the same concentration. The minimum inhibitory concentration (MIC) results for the complexes also showed similar trends against the three bacteria. On the other hand, radical scavenging activities of both Cu(II) and Zn(II) complexes showed half-maximal inhibitory concentrations (IC₅₀) of 4.72 and 8.2 μg/mL, respectively, while ascorbic acid (a positive control) has a value of 4.28 μg/mL. The Cu(II) complex exhibited better communication with the positive control, indicating its potential use for biological activities. The calculated and in silico molecular docking results also strongly support the experimental results.

Scheme 1. Proposed Synthesis Reaction Scheme of (A) Ligand (H₂L) and (B) Zn(II) and Cu(II) Complexes

Figure 1

Comparison of the experimental absorption wavelengths with the corresponding B3LYP-GD3/6-311++G(d,p)/LanL2DZ/IEF-PCM/Methanol-calculated results of the Zn(II) and Cu(II) complexes. The calculated absorption maxima red-shifted by 20 nm for better comparison with the experimental results.

Figure 2

(a) HOMO and LUMO of the ligand and its metal complexes. (b) Spin density plots of the Cu(II) complex. The HOMO–LUMO energies are in hartrees.

Figure 3

Fluorescence spectra of the free ligand (H₂L) and its (1) Zn(II) and (2) Cu(II) complexes.

Figure 4

Energy-dispersive X-ray spectra of (A) Zn(II), (B) Cu(II), and (C) H₂L(II). SEM images of (D) Zn(II) and (E) Cu(II) complexes and (F) H₂L(II).

Figure 5

TGA and DTA curves of (A) Zn(II) and (B) Cu(II) complexes.

Figure 6

Mean inhibition zone of bacterial activity of the titled compounds. n = 3. Error bars indicate standard deviation.

Figure 7

(A) Percent of free radical scavenging activities and (B) IC₅₀ of titled compounds.

Figure 8

Binding interactions of complex 1 against P. aeruginosa LasR.DNA (PDB: 2UV0).

Figure 9

Binding interactions of complex 2 against P. aeruginosa LasR.DNA (PDB: 2UV0).